The Effect of Nitroglycerin Infusion Rate on Cerebral Rewarming During Hypothermic Coronary Artery Bypass Grafting

NCT03251599 | Completed Phase 4 DMC

• 1 other identifier: 2017/5
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

Glyceryl trinitrate is used in coronary artery bypass grafting surgery. This surgery frequently employs hypothermic cardiopulmonary bypass, where the whole body is cooled down to 28-32 °C to arrest the heart, and protect the organs from ischemic insult. When the cardiac repair or grafting is done, the body is warmed to 37 °C. During this "rewarming period", the heart has to beat against the vessels, all of which are constricted due to hypothermia. To overcome this constriction of the vessels, and decrease the workload of the heart, glyceryl trinitrate is infused. This drug causes significant dilatation in arteries and veins, which allows the heart to pump the blood with less force. The dilatation of the vessels also allows the body to rewarm more easily. The investigators' concern is whether increased infusion rates of glyceryl trinitrate may cause uncontrolled rewarming of the brain or not. The investigators will measure the temperature of the brain using a temperature probe located in the nasal cavity. The temperature will be recorded at each minute during the the rewarming period. Results of two commonly used infusion rates of glyceryl trinitrate will be compared.

Conditions

Coronary Artery Bypass; Cardiopulmonary Bypass

Keywords

peak temperature; rewarming rate; surgical outcomes

Outcome Measures

Primary Outcomes (2)

• Nasopharyngeal temperature > 37 °C

  If the nasopharyngeal temperature is \> 37 °C by the time the esophageal temperature reached 37 °C.

  Rewarming period of cardiopulmonary bypass, usually 30 - 45 minutes

• Time to 37 °C

  Time required to reach an esophageal temperature of 37 °C.

  Rewarming period of cardiopulmonary bypass, usually 30 - 45 minutes

Secondary Outcomes (7)

• Adverse event: Regional cerebral oxygen saturation

  Rewarming period of cardiopulmonary bypass, usually 30 - 45 minutes

• Length of Intensive Care Unit stay

  Postoperative period from entrance to Intensive Care Unit until the date of death from any cause or discharge from Intensive Care Unit, whichever came first, assessed up to 1 month

• Length of hospital stay

  Postoperative period from entrance to Intensive Care Unit until the date of death from any cause or discharge from hospital, whichever came first, assessed up to 3 months

• Frequency of atrial fibrillation

  Postoperative period from entrance to Intensive Care Unit until the date of death from any cause or discharge from hospital, whichever came first, assessed up to 3 months

• Frequency of low cardiac output syndrome

  Postoperative period from entrance to Intensive Care Unit until the date of death from any cause or discharge from hospital, whichever came first, assessed up to 3 months

Study Arms (2)

Glyceryl trinitrate 0.2

SHAM COMPARATOR

Drug Intervention Generic name: Glyceryl trinitrate Dosage form: Ampoule for intravenous infusion Dosage: 0.2 mcg/kg/minute Frequency and duration: The infusion will start as soon as the rewarming period starts, will continue throughout the operation and throughout the first 24 hours of the postoperative period.

Drug: Glyceryl trinitrate 0.2

Glyceryl trinitrate 0.5

ACTIVE COMPARATOR

Drug Intervention Generic name: Glyceryl trinitrate Dosage form: Ampoule for intravenous infusion Dosage: 0.5 mcg/kg/minute Frequency and duration: The infusion will start as soon as the rewarming period starts, will continue throughout the operation and throughout the first 24 hours of the postoperative period.

Drug: Glyceryl trinitrate 0.5

Interventions

Glyceryl trinitrate 0.2 DRUG

These patients will receive glyceryl trinitrate infusion at a rate of 0.2 mcg/kg/min throughout the rewarming period of cardiopulmonary bypass, which usually lasts for 30-45 minutes.

Also known as: Nitroglycerin, Perlinganit

Glyceryl trinitrate 0.2

Glyceryl trinitrate 0.5 DRUG

These patients will receive glyceryl trinitrate infusion at a rate of 0.5 mcg/kg/min throughout the rewarming period of cardiopulmonary bypass, which usually lasts for 30-45 minutes.

Also known as: Nitroglycerin, Perlinganit

Glyceryl trinitrate 0.5

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients who are scheduled for on-pump coronary artery bypass grafting surgery

You may not qualify if:

• Administration of vasopressors during rewarming period

Sponsors & Collaborators

• Recep Tayyip Erdogan University: lead

Study Sites (1)

Recep Tayyip Erdogan University, Medical Faculty

Rize, 53100, Turkey (Türkiye)

Location

Related Publications (5)

• Johansson BW. The hibernator heart--nature's model of resistance to ventricular fibrillation. Cardiovasc Res. 1996 May;31(5):826-32. doi: 10.1016/0008-6363(95)00192-1.

  PMID: 8763414 BACKGROUND

• Michenfelder JD, Milde JH. The relationship among canine brain temperature, metabolism, and function during hypothermia. Anesthesiology. 1991 Jul;75(1):130-6. doi: 10.1097/00000542-199107000-00021.

  PMID: 2064037 BACKGROUND

• Hori D, Everett AD, Lee JK, Ono M, Brown CH, Shah AS, Mandal K, Price JE, Lester LC, Hogue CW. Rewarming Rate During Cardiopulmonary Bypass Is Associated With Release of Glial Fibrillary Acidic Protein. Ann Thorac Surg. 2015 Oct;100(4):1353-8. doi: 10.1016/j.athoracsur.2015.04.006. Epub 2015 Jul 7.

  PMID: 26163357 BACKGROUND

• Engelman R, Hammon JW, Baker RA, Shore-Lesserson L. Rapid Rewarming During Cardiopulmonary Bypass Is Associated With Cerebral Injury. Ann Thorac Surg. 2016 May;101(5):2026-7. doi: 10.1016/j.athoracsur.2015.11.021. No abstract available.

  PMID: 27106452 BACKGROUND

• Grigore AM, Grocott HP, Mathew JP, Phillips-Bute B, Stanley TO, Butler A, Landolfo KP, Reves JG, Blumenthal JA, Newman MF; Neurologic Outcome Research Group of the Duke Heart Center. The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery. Anesth Analg. 2002 Jan;94(1):4-10, table of contents. doi: 10.1097/00000539-200201000-00002.

  PMID: 11772792 BACKGROUND

MeSH Terms

Interventions

Nitroglycerin

Intervention Hierarchy (Ancestors)

Nitro Compounds; Organic Chemicals

Study Officials

• Başar Erdivanlı, M.D.

  Recep Tayyip Erdogan University Medical Faculty

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The randomization will be via enclosed envelope technique. The anesthetic management of the patient will be provided by an anesthesiologist other than the investigator. This anesthesiologist will not be blinded to the dose of the study drug, and will be responsible from the administration of the appropriate dose of the study drug. The perfusionist, who is the main care provider during the rewarming period of the cardiopulmonary bypass, will be blinded to the dose of the study drug. The investigator will be blinded, and will be responsible from the collection, and validation of the data.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Asst. Prof. of Anesthesiology and Reanimation

Model Details: Intervention type is drug dosage. Patients will be assigned to 2 arms, where they will receive different doses of the same drug. The study will end when both of the arms will have at least 48 patients each.

Study Record Dates

• First Submitted: August 1, 2017
• First Posted: August 16, 2017
• Study Start: August 16, 2017
• Primary Completion: November 22, 2017
• Study Completion: November 22, 2017
• Last Updated: December 22, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)